Human missions to Mars present several major challenges that must be overcome, including delivering multiple large mass and volume elements, keeping the crew safe and productive, meeting cost constraints, and ensuring a sustainable campaign. Traditional methods for executing human Mars missions minimize or eliminate in-space assembly, which provides a narrow range of options for addressing these challenges and limits the types of missions that can be performed. This paper discusses recent work to evaluate how the inclusion of in-space assembly in space mission architectural concepts could provide novel solutions to address these challenges by increasing operational flexibility, robustness, risk reduction, crew health and safety, and sustainability. A hierarchical framework is presented to characterize assembly strategies, assembly tasks, and the required capabilities to assemble mission systems in space. The framework is used to identify general mission system design considerations and assembly system characteristics by assembly strategy. These general approaches are then applied to identify potential in-space assembly applications to address each challenge. Through this process, several focus areas were identified where applications of in-space assembly could affect multiple challenges. Each focus area was developed to identify functions, potential assembly solutions and operations, key architectural trades, and potential considerations and implications of implementation. This paper helps to identify key areas to investigate were potentially significant gains in